rs1555769166
Variant names:
Variant summary
Our verdict is Pathogenic. The variant received 10 ACMG points: 10P and 0B. PVS1PP5_Moderate
The NM_006949.4(STXBP2):c.212_213delTG(p.Leu71ArgfsTer46) variant causes a frameshift change. The variant allele was found at a frequency of 0.00000479 in 1,461,500 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Pathogenic (★). Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: not found (cov: 33)
Exomes 𝑓: 0.0000048 ( 0 hom. )
Consequence
STXBP2
NM_006949.4 frameshift
NM_006949.4 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 6.35
Publications
0 publications found
Genes affected
STXBP2 (HGNC:11445): (syntaxin binding protein 2) This gene encodes a member of the STXBP/unc-18/SEC1 family. The encoded protein is involved in intracellular trafficking, control of SNARE (soluble NSF attachment protein receptor) complex assembly, and the release of cytotoxic granules by natural killer cells. Mutations in this gene are associated with familial hemophagocytic lymphohistiocytosis. Alternatively spliced transcript variants encoding different isoforms have been noted for this gene. [provided by RefSeq, Jan 2013]
STXBP2 Gene-Disease associations (from GenCC):
- familial hemophagocytic lymphohistiocytosis 5Inheritance: AR, AD Classification: DEFINITIVE, STRONG, LIMITED Submitted by: Ambry Genetics, ClinGen, Labcorp Genetics (formerly Invitae)
- hereditary hemophagocytic lymphohistiocytosisInheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
- microvillus inclusion diseaseInheritance: AR Classification: LIMITED Submitted by: Ambry Genetics
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ACMG classification
Classification was made for transcript
Our verdict: Pathogenic. The variant received 10 ACMG points.
PVS1
Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
PP5
Variant 19-7639772-CTG-C is Pathogenic according to our data. Variant chr19-7639772-CTG-C is described in ClinVar as Pathogenic. ClinVar VariationId is 538150.Status of the report is criteria_provided_single_submitter, 1 stars.
Variant Effect in Transcripts
ACMG analysis was done for transcript: NM_006949.4. You can select a different transcript below to see updated ACMG assignments.
RefSeq Transcripts
| Selected | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| STXBP2 | NM_006949.4 | MANE Select | c.212_213delTG | p.Leu71ArgfsTer46 | frameshift | Exon 4 of 19 | NP_008880.2 | ||
| STXBP2 | NM_001272034.2 | c.212_213delTG | p.Leu71ArgfsTer57 | frameshift | Exon 4 of 19 | NP_001258963.1 | |||
| STXBP2 | NM_001127396.3 | c.212_213delTG | p.Leu71ArgfsTer43 | frameshift | Exon 4 of 19 | NP_001120868.1 |
Ensembl Transcripts
| Selected | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| STXBP2 | ENST00000221283.10 | TSL:1 MANE Select | c.212_213delTG | p.Leu71ArgfsTer46 | frameshift | Exon 4 of 19 | ENSP00000221283.4 | ||
| STXBP2 | ENST00000414284.6 | TSL:1 | c.212_213delTG | p.Leu71ArgfsTer43 | frameshift | Exon 4 of 19 | ENSP00000409471.1 | ||
| STXBP2 | ENST00000597068.5 | TSL:1 | n.212_213delTG | non_coding_transcript_exon | Exon 4 of 19 | ENSP00000471327.1 |
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
33
GnomAD4 exome AF: 0.00000479 AC: 7AN: 1461500Hom.: 0 AF XY: 0.00000275 AC XY: 2AN XY: 727026 show subpopulations
GnomAD4 exome
AF:
AC:
7
AN:
1461500
Hom.:
AF XY:
AC XY:
2
AN XY:
727026
show subpopulations
African (AFR)
AF:
AC:
0
AN:
33470
American (AMR)
AF:
AC:
0
AN:
44712
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
26136
East Asian (EAS)
AF:
AC:
0
AN:
39700
South Asian (SAS)
AF:
AC:
0
AN:
86216
European-Finnish (FIN)
AF:
AC:
0
AN:
53388
Middle Eastern (MID)
AF:
AC:
0
AN:
5546
European-Non Finnish (NFE)
AF:
AC:
7
AN:
1111964
Other (OTH)
AF:
AC:
0
AN:
60368
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.475
Heterozygous variant carriers
0
1
1
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2
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0.00
0.20
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0.60
0.80
0.95
Allele balance
Age Distribution
Exome Het
Variant carriers
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Age
GnomAD4 genome
GnomAD4 genome
Cov.:
33
ClinVar
ClinVar submissions as Germline
Significance:Pathogenic
Revision:criteria provided, single submitter
Pathogenic
VUS
Benign
Condition
1
-
-
Familial hemophagocytic lymphohistiocytosis 5 (1)
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
PhyloP100
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
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